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5 Sonography ofLymph Nodes intheNeck
Fig. 5.34 Indeterminate
CLNs are lacking a hilum and
show at least one of the
following characteristics: (1)
rather a round shape; (2) an
increased short axis (≥8mm
in level II and ≥5mm in
levels III and IV); and/or (3)
an increased central
vascularization
77
Fig. 5.35 Suspicious CLNs
elicit at least one of the
following characteristics: (1)
microcalcications, (2)
partially cystic appearance,
(3) peripheral or diffusely
increased vascularization,
and/or (4) hyperechoic,
thyroid-like looking tissue
57–93%; 30–87%, 43–95%; 37%, 70%, respectively
(Fig.5.37)) but therefore have higher negative predictive values (NPVs) and also higher PPVs (31–70%, 77–80%;
38–84%, 66–96%; 45%, 63%, respectively) while rarely occur
in normal CLNs (1–18%; 4–17%; 4–36%, respectively).
Qualitative/quantitative elastographic assessment
Experience with US elastography (USE) is limited, with sensitivities of 83–85% and specicities of 98–100% [138,
139]. Nevertheless, USE could be applied selectively in nod-
ules with indeterminate or equivocal US appearances and
78
Fig. 5.36 Especially microcalcications and cystic transformation are
strong indicators for malignancy since these do not occur in normal
CLNs
Fig. 5.37 Peripheral vascularization, hyperechogenicity, and round
shape do have moderate sensitivity and specicity, respectively, but
therefore have higher negative and positive predictive values, which
rarely occur in normal CLNs
may improve decision-making for US-guided FNAC by
upgrading or downgrading the risk of malignancy.
Ultrasound-guided ne-needle aspiration (USFNA) and
ultrasound-guided core biopsy (USCB) cytology The
conrmation of malignancy in CLNs is achieved by
US-guided FNA for cytology and/or measurement of thyroglobulin (Tg) in the needle washout (Table5.7). A Tg concentration <1 ng/mL is reassuring; the probability of N1
disease increases with higher Tg levels [140]. This FNA
measurement of Tg is likely to be valid even in patients with
circulating anti-Tg autoantibodies [141, 142], although one
study scrutinizes the validity of this measurement in patients
J. E. Meyer
Table 5.7 Recommendation for the use of ultrasound-guided ne-
needle aspiration (FNA) cytology in CLNs of patients with thyroid
cancer
Strength of
recommendation/
Recommendation for
(A) Preoperative neck US for cervical
(central and especially lateral neck
compartments) lymph nodes is
recommended for all patients undergoing
thyroidectomy for malignant or
suspicious-for-malignancy cytologic or
molecular ndings
(B) US-guided FNA of sonographically
suspicious lymph nodes ≥8–10mm in
the smallest diameter should be
performed to conrm malignancy, if this
would change management
(C) The addition of FNA thyroglobulin (Tg)
washout in the evaluation of suspicious
cervical lymph nodes is appropriate in
selected patients, but interpretation may
be difcult in patients with an intact
thyroid gland
quality of evidence
Strong
recommendation
Moderate-quality
evidence
Strong
recommendation
Moderate-quality
evidence
Weak
recommendation
Low-quality
evidence
with anti-Tg autoantibodies [143]. Tg washout may be helpful, particularly in cases in which the lymph nodes are cystic,
cytologic evaluation of the lymph node is inadequate, or the
cytologic and sonographic evaluations are divergent (such as
normal cytologic biopsy of a large lymph node with microcalcications) [144]. In a retrospective study, additional
FNA with Tg washout measurements (FNA-Tg) helped to
diagnose a metastatic lymph node with one or two suspicious
US features, but it did not offer incremental benet for those
lymph nodes with highly suspicious US features in which
FNA alone was sufcient for diagnosis. Two recent systematic reviews showed that false-positive Tg washout may particularly occur in lymph nodes in the central compartment
when the thyroid gland is still present [145, 146]; therefore
an FNA-Tg cutoff of 32ng/mL is suggested [146]. Others
have interpreted FNA-Tg in the context of serum Tg and
TSH in these patients [147, 148], so standardization of the
interpretation of Tg washout is urgently required for determining the prognosis and tailoring treatment for patients
with differentiated thyroid cancer. However, removal of the
primary thyroid tumor and accessible locoregional disease
remains an important component of initial treatment even in
most patients with metastatic disease [149].
5.1.8 Malignant Lymphoma Nodes
Characteristics Elliptical, homogenous with intranodal
reticulation, hilum present, sharp borders, longitudinal diam-
5 Sonography ofLymph Nodes intheNeck
eter<18mm, minimal cross-sectional diameter >8–10mm,
color/Doppler mode mixed vascularization.
Plane grayscale ultrasonography Lymph nodes can be
affected by either Hodgkin’s or non-Hodgkin’s lymphoma.
Affected nodes can appear in any level of the neck, unilaterally or bilaterally. It is not possible to distinguish between
both lymphoma forms by sonography alone. The diameter of
lymphomatous cervical nodes is not an accurate criterion for
differentiating lymphomatous from normal or other pathologic CLNs, because they can vary signicantly [150].
Typically, lymphomatous nodes are enlarged, with a minimal
diameter of 10 mm or larger in the beginning [151, 152];
gradual and substantial reduction in size during treatment
indicates a good treatment response [153].
A lymphomatous node is usually round and well-dened;
it appears hypoechoic and lacks an echogenic hilum
(Figs. 5.38 and 5.39) [152, 154, 155]. These features are
unspecic and therefore may not be useful US criteria to differentiate lymphoma from metastatic CLNs.
Although previous studies suggested that a pseudocystic
appearance with posterior acoustic enhancement is characteristic of lymphomatous nodes (Fig.5.40) [152, 154, 155],
with the use of newer high-resolution transducers, pseudocystic appearance is not often seen, but intranodal reticulation, a micronodular echo pattern, is commonly found
(Figs.5.41 and 5.42) [156].
Lymphomatous CLNs seldom show a real cystic necrosis
unless the disease is advanced or the patient has received previous radiation or chemotherapy [151]. Similarly, intranodal
dense calcication with posterior acoustic shadowing is
uncommon and may be found only after treatment [157].
79
Fig. 5.39 A characteristic longitudinal plane of a chain of hypoechoic
lymphomatous CLNs packed back to back of each others
Doppler ultrasonographic assessment of intranodal vascular resistance
Lymphomatous nodes tend to have a
mixed vasculature (hilar and peripheral), whereas an isolated
peripheral vasculature is uncommon (Fig.5.43) [157]. The
relatively high incidence of hilar vascularization in lymphomatous nodes is believed to be associated with the combination of malignant lymphatic and vascular hyperplasia of
preexisting immune cells and vessels (Fig. 5.44). Since a
peripheral vascularization is characteristic for malignant
nodes, its presence is highly suggestive of malignancy, with
a sensitivity of 67% and a specicity of 100% for distinguishing lymphomatous from reactive lymph nodes [158].
Furthermore, this sign is also used for monitoring of therapeutic success. Reduced intranodal vascularization is a sign of
good treatment response in patients with non-Hodgkin lymphoma during chemotherapy, whereas lymph nodes with persistent vasculature tend to have poor clinical outcome [153].
The application of power Doppler US in the assessment of
cervical nodes might not be necessary for all cases in routine
clinical practice, because grayscale ultrasonography with the
features described above already achieves a high sensitivity
(95%) and high specicity (83%) in differentiating metastatic
and nonmetastatic nodes [159]. Power Doppler US is useful in
patients for whom grayscale ultrasonography is equivocal, however, and it improves diagnostic accuracy (Video 5.8) [159].
As with metastatic lymph nodes, the role of vascular
resistance in the assessment of lymphomatous nodes is
unclear, and further research is needed [31, 35, 160].
Fig. 5.38 A lymphomatous node is usually round-shaped, well-
dened, appears hypoechoic, and without an echogenic hilum. These
features are unspecic and therefore may not be useful ultrasonographic
criteria to differentiate lymphoma from metastatic CLNs
Qualitative elastographic assessment Tan etal. recently
investigated elastography in lymphomatous nodes and
reported that lymphomatous malignant and benign nodes
could not be distinguished by the elastographic score alone;
both show similar elastographic characteristics, whereas
solid malignant lymphadenopathies are more stiff [43].
80
Fig. 5.40 Previous studies
had suggested that
pseudocystic appearance with
posterior acoustic
enhancement is characteristic
features of lymphomatous
nodes
J. E. Meyer
Fig. 5.41 With the use of
newer high-resolution
transducers, pseudocystic
appearance is not often seen,
while intranodal reticulation,
a micronodular echopattern, is
commonly found in
lymphomatous nodes
Ultrasound-guided ne-needle aspiration (USFNA)
and ultrasound-guided core biopsy (USCB)
cytology Although USFNA or USCB cytology is very
useful in the diagnosis of malignancies, in cases of lym-
phomatous nodes, surgical excision of the lymph node
and a specied immunochemistry are mandatory to determine the subtype of lymphomas and plan the treatment
regimen [128].
5 Sonography ofLymph Nodes intheNeck
Fig. 5.42 Pseudocystic
appearance of lymphpmatous
CLN
81
Fig. 5.43 Lymphomatous nodes tend to have a mixed vasculature
(hilar and peripheral), whereas an isolated peripheral vasculature is
uncommon
5.2 Regional Dierential Diagnoses
Lymph node compartments are separated into levels and sublevels according to the last CLN classication of the
American Head and Neck Society (Fig. 5.45) [161, 162].
Level VI contains the thyroid gland and the adjacent nodes
bordered superiorly by the hyoid bone, inferiorly by the brachiocephalic artery dened by the suprasternal notch, and
laterally on each side by the carotid sheaths. The level II, III,
Fig. 5.44 The relatively high incidence of hilar vascularization in lym-
phomatous nodes is believed to be associated with the combination of
malignant lymphatic and vascular hyperplasia of preexisting immune
cells and vessels. Since a peripheral vascularization is characteristic for
malignant nodes, its presence is highly suggestive for distinguishing
lymphomatous from reactive lymph nodes
and IV nodes are arrayed along the jugular veins on each
side, bordered anteromedially by level VI and laterally by the
posterior border of the sternocleidomastoid muscle. The
level III nodes are bounded superiorly by the level of
thehyoid bone and inferiorly by the cricoid cartilage; level II
is above level III, and level IV is below it. The level I node
compartment includes the submental and submandibular
82
Sternocleidomastoid
e
IAAAIAA
A
Fig. 5.45 Lymph node
compartments are separated
into levels and sublevels
according to the last CLN
classication of the American
Head and Neck Society by
Robbins etal. [162]
Cranial accessory
nerve
Internal jugular vein
IIB
IIA
J. E. Meyer
Submandibular
gland
IB
IA
Anterior belly of
the digastric muscl
Hyoid bone
nodes, above the hyoid bone and anterior to the posterior
edge of the submandibular gland. Finally, the level V nodes
are in the posterior triangle, lateral to the lateral edge of the
sternocleidomastoid muscle and medial to the trapezius muscle. Level VII includes the paratracheal and pretracheal superior mediastinal CLNs above the level of the brachiocephalic
artery; it lies just caudal to level VI.Levels I, II, and V can be
further subdivided into parts A and B, as noted in Fig.5.45.
Table5.8 lists the primary tumor sites most likely to metastasize to each level.
5.2.1 Central/Anterior Lymphadenopathy
Head andNeck Squamous Cell Carcinoma
(HNSCC)
The Delphian lymph node is frequently involved in metastatic laryngeal squamous cell carcinoma of the glottic and
subglottic area and is found anterior to the thyroid cartilage.
Furthermore, cancers arising from the apex of the piriform
sinus and cervical esophagus metastasize to the anterior
compartment group (level VI). Therefore, US investigation
muscle
Spinal accessory
nerve
VA
III
VI
IV
VB
Carotid artery
Cricoid cartilage
of the neck should always involve level VI in laryngeal,
hypopharyngeal, and cervical esophageal cancer.
Infrequently, level VII can also be involved, especially in
advanced cancer of these locations.
Thyroid Cancer
A systematic sonographic evaluation of the anterior (and lateral) CLN levels VI and VII should be performed whenever
thyroid nodules are detected. If US identies suspicious
CLNs, an US-guided FNAC of the suspicious lymph node
(and the thyroid nodule) should be performed, and a washout
for Tg measurement is indicated [131]. This approach also
warrants US-guided FNA of nodules measuring less than a
centimeter.
5.2.2 Lateral Lymphadenopathy
Head andNeck Squamous Cell Carcinoma
Submental CLNs (sublevel IA) are at greatest risk for harboring metastases from cancers arising from the oor of the
mouth, anterior oral tongue, anterior mandibular alveolar
5 Sonography ofLymph Nodes intheNeck
Table 5.8 Local distribution of underlying diseases to CLN levels
CLN
level Anatomic regions Primary drainage sites/origins
IA Submental lymph
nodes
IB Submandibular
lymph nodes
IIA Anterior cervical Oral cavity, nasal cavity, nasopharynx,
IIB Upper jugular Oral cavity, nasal cavity, nasopharynx,
III Middle jugular Oral cavity, nasopharynx, oropharynx,
IV Lower jugular Hypopharynx, cervical esophagus, and
VA Upper accessory Nasopharynx, oropharynx, and
VB Lower accessory Nasopharynx, oropharynx, and
VI Prelaryngeal and
pretracheal/
paratracheal
VII Superior
mediastinal
Floor of mouth, anterior oral tongue,
anterior mandibular alveolar ridge, and
lower lip
Oral cavity, anterior nasal cavity, soft
tissue structures of the midface, and
submandibular gland
Non-tuberculous lymphadenopathies
oropharynx, hypopharynx, larynx, and
parotid gland
Thyroid gland (papillary cancer),
tuberculous lymphadenopathies
oropharynx, hypopharynx, larynx, and
parotid gland
Thyroid gland (papillary cancer),
tuberculous lymphadenopathies
hypopharynx, and larynx
Thyroid gland, tuberculous
lymphadenopathies
larynx
Thyroid gland, tuberculous
lymphadenopathies
cutaneous structures of the posterior
scalp and neck, tuberculous
lymphadenopathies
cutaneous structures of the posterior
scalp and neck, tuberculous
lymphadenopathies
Glottic and subglottic area, apex of the
piriform sinus, and cervical esophagus
Thyroid gland
Glottic and subglottic area, apex of the
piriform sinus, and cervical esophagus
Thyroid gland
83
Fig. 5.46 Submandibular metastasis (level IB) from a cancer arising
from the oral cavity
Fig. 5.47 Upper jugular metastasis (level IIA) from a cancer arising
from the oropharynx
ing metastases from cancers arising from the hypopharynx,
cervical esophagus, and larynx (Fig.5.49) [162].
ridge, and lower lip, whereas submandibular CLNs (sublevel
IB) harbor metastases from cancers arising from the oral
cavity, anterior nasal cavity, soft tissue structures of the midface, and submandibular gland (Fig.5.46) [161].
The upper jugular CLN chain (including sublevels IIA
and IIB) bears metastases from cancers arising from the oral
cavity, nasal cavity, nasopharynx, oropharynx, hypopharynx,
larynx, and parotid gland (Fig. 5.47), whereas the middle
jugular lymph nodes (level III) may be involved by cancers
arising from the oral cavity, nasopharynx, oropharynx,
hypopharynx, and larynx (Fig. 5.48). More caudally, the
lower jugular CLNs (level IV) are at greatest risk for harbor-
Thyroid Gland Cancer
The location of the lymph nodes may also be useful for
decision- making in thyroid gland carcinomas. Malignant
lymph nodes are much more likely to occur in levels III, IV,
and VI than in level II [21, 22], although this may not be true
for papillary thyroid cancer (PTC) tumors arising in the upper
pole of the thyroid, which have a higher propensity to demonstrate skip metastases to levels III and II (Fig.5.50) [163].
Non-tuberculous Lymphadenopathy
Non-tuberculous lymphadenopathy involves primarily children under 5 years of age and submandibular (level IB), preauricular, and, rarely, parotid CLN levels.
84
Fig. 5.48 Middle jugular
metastasis (level III) arising
from a cancer of the larynx
J. E. Meyer
Fig. 5.49 Lower jugular metastasis (level IV) arising from a cancer of
the hypopharynx
Tuberculous Lymphadenopathy
Tuberculous lymphadenopathy shows up in adults with a
unilateral enlarged CLN without pain or tenderness; it usually involves the lymph nodes of levels II–IV, level V, and the
supraclavicular fossa [47, 50].
5.2.3 Posterior Lymphadenopathy
HNSCC Lymph Node Metastases
The posterior triangle group, which includes sublevels VA and
VB, is at greatest risk for harboring metastases from cancers
arising from the nasopharynx, oropharynx, and cutaneous structures of the posterior scalp and neck (Figs.5.51 and 5.52) [161].
In cases of cutaneous cancers, often the parotid gland is the rst
place of metastasis.
Tuberculous Lymphadenopathy
Tuberculous lymphadenopathy usually is an unilateral
lymphadenopathy without pain or tenderness; it usually
involves the lymph nodes of levels II–IV, level V, and the
supraclavicular fossa [47, 50].
5.3 Cystic/Necrotic Lymphadenopathy
5.3.1 Inammatory Lymphadenopathies
Cystic/necrotic transformation is absent in reactive lymphadenopathy and is infrequent in infectious mononucleosis,
whereas liquid areas in suppurative/necrotizing lymphadenopathy or abscesses are obligatory. Moreover, liquefaction
is characteristic of tuberculous lymphadenopathy (“collar
stud” abscess) and non-tuberculous lymphadenopathy (stage
II, intranodal cystic necrosis).
5.3.2 Malignant Lymphadenopathies
Cervical metastases are often the rst sign in patients with
carcinoma of the head and neck (HNSCC) or other origins.
These metastatic nodes frequently undergo cystic degeneration and may be difcult to distinguish from other cystic
lesions of the head and neck (Fig.5.53). In the presence of a
primary head and neck cancer, a nodal necrosis is the most
5 Sonography ofLymph Nodes intheNeck
Fig. 5.50 PTC skip
metastasis arising from the
upper pole of the ipsilateral
thyroid to level II/III
85
Fig. 5.51 A non-tuberculous
lymphadenopathy in the
submandibular level (level IB)
valuable sign of metastatic involvement, with specicity
between 95% and 100% [164]. The following paragraphs
describe some special entities.
HPV-Positive Metastases
Cervical metastases from primaries in the oropharynx have
been shown to be more likely to undergo cystic changes
than squamous cell carcinoma from other head and neck
sites [166, 167]. This nding was one of the rst hints of a
new entity of HNSCCs, the HPV-positive HNSCC
(Fig.5.54). HPV-positive HNSCC show regularly small primaries, most of which are hidden in the palatine tonsil or the
base of the tongue, with many CLN metastases, which may
be cystic. In these cases, especially if no primary is seen,
86
J. E. Meyer
Fig. 5.52 Metastasis in the posterior triangle group arising from a cancer of the nasopharynx
a
Fig. 5.53 (a–c) Cervical metastases are often the rst sign in patients
with carcinoma of the head and neck and frequently undergo cystic
degeneration. This nodal necrosis is the most valuable sign of metastatic involvement. (a) A small and in the beginning indeterminate
CLN. (b) Within 2months this CLN elicited progressive growth and
cystic degeneration. (c) Only 1 week later, further growth could be
detected and nodal necrosis is apparent